1. Field of the Invention
The present invention is concerned with novel ascorbate 2-polyphosphate esters, as well as methods for the synthesis of such esters and the corresponding salts thereof. More particularly, it is concerned with L-ascorbate 2-triphosphate which has been shown to be a new stable form of vitamin C, and which can be prepared and recovered at lower cost than prior stable forms of vitamin C such as the monophosphate form, L-ascorbate 2-phosphate.
2. Description of the Prior Art
L-Ascorbic acid and D-isoascorbic acid are two stereoisomeric six-carbon ascorbic acids that have many uses in pharmaceuticals, food, feed, and a variety of minor products. The utility of L-ascorbic acid arises mainly from its vitamin C activity, strong reducing power, and low toxicity, while the use of D-isoascorbic acid depends on its strong reducing power and its low cost compared to L-ascorbic acid. The use of D-isoascorbic acid in foods and feeds is restricted because of its low vitamin C activity and its antagonist effect on the absorption of L-ascorbic acid in the digestive tract. Because L-ascorbic acid reduces oxygen, the vitamin is often lost as it contacts air during processing and storage of food and feed. On long term storage in an acid medium, especially under heat, L-ascorbic acid is also destroyed by a second process involving dehydration of the molecule. Thus, nutritionists and food scientists have long sought a form of vitamin C that is stable to air and acid, prticularly to air.
Two methods have been used in the past to increase the stability of ascorbic acid, encapsulating the solid crystals of L-ascorbic acid, and chemically substituting the ene-diol functional group on the molecule. Fat-encapsulated forms of vitamin C have several shortcomings. The larger the crystals of L-ascorbic acid that are coated, the more difficult it is to distribute the coated vitamin in a food or feed, especially if the food or feed is finely divided. On the other hand, the smaller the crystals of L-ascorbic acid, the less perfect the encapsulation. Typically, crystals of 250-300 micrometers (50-60 mesh) are coated with 15-50% add-on fat. During processing of food or feed, the protective fat coating may be melted away or rubbed off the crystals. Encapsultated particles are coated with triglycerides that melt at 50.degree.-60.degree. C.; or with wax such as caranauba, which melts at about 85.degree. C. It is likely that caranauba coated L-ascorbic acid is not digestible, and is therefore unavailable to animals. L-Ascorbic acid has also been encapsultaed with polymers that slowly dissolve to release vitamin C. During processing of food or feeds, these types of coated forms may give substantial losses of the vitamin.
Chemically modified forms of L-ascorbic acid circumvent the problems of stability, particlesize, and biological availability of coated forms. The chemically modified forms are stabilized against oxygen by substituting of the 2- or 3-hydroxyl of L-ascorbic acid. Examples of these derivatives include the 2- or 3-methyl ethers, the 2-sulfate ester, the 2-phosphate ester, and the 2,2-bis-(L-ascorbyl) phosphate ester. Of these examples, the 2-phosphate ester of L-ascorbic acid has been shown to be an active form of vitamin C in monkeys, and presumably in other primates such s man (L. J. Machlin et al, Am. J. Clin. Nutr. 32, 1979, p 325). The 2-sulfate ester is not an active source of vitamin C in guinea pigs and monkeys, (L. J. Machlin, Am. J. Clin. Nutr. 29, 1976, p 825), but it is in fish and possibly crustacea (J. E. Halver et al, N.Y. Acad. Sci. 258, 1975, p 81). The methyl esters are only about 5% active in guinea pigs (P. W. Lu et al, J. Ag. Food. Chem. 32, 1984, p 21).
L-Ascorbate 2-phosphate (ASMP) has been known since 1961 when it was first reported by Italian workers (E. Cutolo and A. Larizza, Gazz. Chim. Ital. 91, 1961, p 964). Other investigators have since improved the chemical synthesis of L-ascorbate 2-phosphate so that 86% of the magnesium salt can be isolated in almost pure form without chromatrographic purification starting form L-ascorbic acid (P. A. Seib et al. U.S. Pat. No. 4,179,445, Dec. 18, 1979). Methods to prepare 2,2'-bis-(L-ascorbyl) phosphate are moderately successful (about 30% yield, C. H. Lee, et al, Carbohydrate Res. 67, 1978, p 127), but the vitamin C activity of the diascorbyl phosphate is unknown.
L-Ascorbate 2-pyrophosphate (L-ascorbate 2-diphosphate) has been prepared by reaction of phosphorus oxychloride with 5,6-O-isopropylidene-L-ascorbic in a mixture of water, acetone and pyridine (H. Nomura et al., Chem. Phar. Bull., Japan, 17, 1969, 381). The pyrophosphate ester was obtained in only 5% yield, and it had to purified from three other reaction products using ion-exchange chromatography. The low yield and difficult purification renders L-ascorbate 2-pyrophosphate an impractical source of stable vitamin C for commercial purposes.